p-menth-1-en-4-ol

Endpoint summary

Description of key information

Oral:

In an acute oral toxicity study similar to OECD Guideline 401 in rats (MB Research Lab, 1977), an LD 50 of 1300 mg/kgbw was determined.

Dermal:

In an acute dermal toxicity study similar to OECD Guideline 402 in rabbits (MB Research Lab, 1977), an LD 50 > 2500.0 and < 5000.0 mg/kg bw was determined.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

10 animals/group, no record of bodyweight/gain

GLP compliance:

no

Remarks:

pre-GLP study

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Sample markings: 76-363, 4-TERPINENOL

Species:

rat

Route of administration:

oral: unspecified

Doses:

0.6, 1.22, 2.47, and 5.0 g/kg

No. of animals per sex per dose:

10 per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: at least once a day
- Necropsy of survivors performed: yes

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

1 300 mg/kg bw

Based on:

test mat.

Mortality:

In the 0.6 g/kg dose group one animal died. In the 1.22 g/kg dose group, 4 animals died. In the 2.47 g/kg dose group, 9 animals died and in the 5.0 g/kg dose group, all animals died. In all dose groups, the animals died on day 1 after administration of the test substance.

Clinical signs:

other: Symptomatology Rats: 0.6 g/kg - ataxia, lethargy, tremors, chromorhinorrhea, chromodacryorrhea 1.22 g/kg - lethargy, ptosis, pile-erection chromorhinorrhea 2.47 g/kg - salivation, chromorhinorrhea, ataxia 5.0 g/kg - coma and death

Necroscopy Observations

Dose g/kg	0.6	1.22	2.47	5.0
Lungs dark	1	4	9	9
Liver dark	1	4	8	7
Areas of redness in intestines	1	4	6	6
Kidneys dark	1	2	2	3
Dried blood around eyes			3
Yellow exudate - nose and mouth			3
Portions of intestines yellow			3
Portions of stomach red			3
Bloody urine in bladder			2
Red exudate - mouth			2
Kidneys mottled		3	1

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the conditions chosen and the results obtained, the test substance is considered to be classified as acute toxic category 4 (H302: harmful if swallowed). The LD50 was reported to be 1.3 g/kg.

Executive summary:

An acute toxicity test via the oral route was performed pre-GLP. The test was equivalent or similar to the OECD guideline 401. Ten rats per dose group were treated with 0.6, 1.22, 2.47, and 5.0 g/kg of the test substance of which died at the first observation day 1/10, 4/10, 9/10, and 10/10, respectively. The LD50 was reported to be 1.3 g/kg. Necropsy observations revealed dark lungs, dark liver, dark kidneys, and areas of redness in intestines, among others.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 300 mg/kg bw

Quality of whole database:

Sufficient for the determination of the LD50.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

no record of the body weight/-gain

GLP compliance:

no

Remarks:

pre GLP-Study

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Sample markings 76-363, 4-TERPINENOL

Species:

rabbit

Doses:

1.25, 2.5, and 5.0 g/kg

No. of animals per sex per dose:

4 per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: at least once a day
- Necropsy of survivors performed: yes

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 2 500 - < 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: mortality was observed

Mortality:

In the 5.0 g/kg dose group, 3 animals died within day 1. One more animal died on day 2

Clinical signs:

other: Ataxia and negative righting reflex in 1/each at 5.0 g/kg.

Other findings:

Skin Irritation:
- Redness: 1.25 g/kg: Moderate-2, severe-2
2.5 g/kg - Moderate - l, severe - 3
5.0 g/kg - severe - l
- Edema - moderate in all

Necropsy observations

Dose g/kg	1.25	2.5	5.0
Reddish urine			1
Liver mottled			3
Area of exposure edematous			3
Urine very dark			1
Light eschar formation in exposure area	2	2	1
Areas of lung dark			2
Portions of intestinal wall white			1
Yellow exudate - nose			1
Areas of stomach yellow			1
Heavy eschar formation in area of exposure		1

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Under the conditions chosen, the test substance revealed a LD50 of greater than 2.5 g/kg.

Executive summary:

A dermal toxicity test in rabbits pre-GLP was conducted. The test was equivalent or similar to the OECD guideline 402. Four animals per dose group were treated with 1.25, 2.5, and 5.0 g/kg of the test substance. Three animals and one animal of the highest test group died on the first day of observation and on the second day of observation, respectively. No deaths occurred at the lower dose groups. Systemic effects were observed to be ataxis and negative righting reflex in each animal at 5.0 g/kg. Skin irritation, from moderate to severe, was observed in all animals. The LD50 was reported to be greater than 2.5 g/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Sufficient for classification.

Additional information

Oral:

In the available study (MB Research Lab, 1977) the acute toxic effects of p-menth-1-en-4-ol were investigated after a single oral gavage to rats similar to the OECD Guideline 401. The test substance was administered once orally via gavage to rats (male/female not specified, 10 animals/dose) at doses of 0.6, 1.22, 2.47, and 5.0 g/kg bw. Body weight was not determined. Clinical observations were performed at least once per day during the 14 days observation period and all animals were sacrificed and necropsied at the end of the observation period. Following clinical signs were observed: 0.6 g/kg bw - ataxia, lethargy, tremors, chromorhinorrhea, chromodacryorrhea; 1.22 g/kg bw - lethargy, ptosis, pile-erection chromorhinorrhea; 2.47 g/kg bw - salivation, chromorhinorrhea, ataxia; 5.0 g/kg bw - coma and death. In the 0.6 g/kg dose group, 1 animal died. In the 1.22 g/kg bw dose group, 4 animals died. In the 2.47 g/kg bw dose group, 9 animals died and in the 5.0 g/kg bw dose group, all animals died. In all dose groups, the animals died on day 1 after administration of the test substance.

Based on the mortality, a LD50 of 1300.0 mg/kg bw was determined.

Dermal:

In an acute dermal toxicity study similar to OECD Guideline 402 (MB Research Lab, 1977) groups of adult rabbits (4/dose, sex not specified) were dermally exposed to p-menth-1-en-4-ol at doses of 1.25, 2.5, and 5.0 g/kg bw. Animals then were observed for 14 days. Following treatment related clinical signs were observed: ataxia and negative righting reflex at 5.0 g/kg. No mortality occured in the 1.25 and 2.5 g/kg bw dose group. All (4) animals died within the first two days after test substance application in the 5.0 g/kg bw dose group. A dermal LD50 of > 2500 and < 5000 mg/kg bw was determined.

Specific target organ toxicity - single exposure:

In both oral and dermal acute toxicity studies, effects relating to transient neurodepression were observed. In the acute dermal toxicity study in rabbits, 1 animal at the top dose of 5000 mg/kg bw showed ataxia and negative righting reflex. In the acute oral toxicity study, the high dose animals (5000 mg/kg bw) were comatose and died following test substance administration. Animals in the 2470 and 600 mg/kg bw dose groups showed ataxia, and at 600 and 1220 mg/kg bw additionally lethargy was observed. Taken together, these symptoms indicate transient neurodepression related to test substance administration and justify classification with STOT SE 3, H336 (may cause drowsiness and dizziness).

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008.

An oral LD50 of 1300.0 mg/kg bw was determined. As a result the test substance is considered to be classified for acute oral toxicity (Category 4, H302) under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.

In an acute dermal toxicity study a dermal LD50 > 2500 mg/kg bw was detrmined. Thus, the test substance is not considered to be classified for acute dermal toxicity under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.

Additionally classification for specific target organ toxicity after single exposure (STOT SE 3), H336, is considered justified based on the results observed in acute oral and acute dermal toxicity studies. Thus, the substance is to be classified with STOT SE 3 (H336) under Regulation (EC) 1272/2008 (CLP).